Comparative evaluation of DQ-2511, a novel gastroprokinetic agent,with cisapride in ameliorative action on experimentally induced delayed gastric emptying

We compared the main pharmacological effect of DQ-2511 (3-[[[2-(3,4-dimethoxyphenyl)-ethyl]carbamoyl]methyl]amino -N- methylbenzamide), a novel gastroprokinetic agent, with that of cisapride. Single oral administration of DQ-2511 (3–10 mg kg^?1) caused similar significant improvements to delays in gastric emptying of semi-solid meals evoked by chole-cystokinin-octapeptide (CCK₈: 5 μ kg^?1, i.v.) in monkeys, to that with cisapride (3 mg kg^?1). A 2-week oral treatment of unilaterally vagotomized rats with DQ-2511 (1–10 mg kg^?1) lessened delays in gastric emptying, whereas cisapride (0.3–10 mg kg^?1) had no effect under the same experimental protocols. In anesthetized rats, bolus intravenous injection of either compound (60 μg kg^?1) enhanced gastric motility determined by means of strain gauge force transducers. Electrophysiological investigations revealed that bolus injection of DQ-2511 (6–60 μ kg^?1) depressed the afferent discharge rate of the ventral gastric branch of the vagus nerve, while cisapride showed no effect. These results suggest that the mechanism of ameliorative action of DQ-2511 on delayed gastric emptying may differ from that of cisapride.